Multiple myeloma is a cancer originating in the plasma cells, a type of white blood cell found in the bone marrow. These abnormal cells can accumulate, crowding out healthy blood cells and producing dysfunctional proteins. The primary goal of treatment for multiple myeloma is to achieve remission, which signifies a significant reduction or complete disappearance of cancer signs and symptoms. This marks a period where the disease is under control, improving a patient’s quality of life.
Understanding Remission Levels
Remission in multiple myeloma is not a singular state; instead, it exists along a spectrum, indicating varying degrees of disease control. A Partial Response (PR) signifies a substantial reduction in myeloma markers, typically a decrease of 50% or more in M-protein levels in the blood or urine. This also means a reduction in tumor size by at least 50% if present.
A Very Good Partial Response (VGPR) represents a more substantial decrease in disease markers than a PR, indicating a 90% or greater reduction in M-protein levels or a urine M-protein level below 100 mg over 24 hours. A Complete Response (CR) means no detectable M-protein in the blood or urine using standard tests, along with fewer than 5% plasma cells in the bone marrow.
A Stringent Complete Response (sCR) builds upon CR criteria by requiring a normal free light chain ratio and the absence of clonal plasma cells in the bone marrow as confirmed by more sensitive tests. The most sensitive measure, Minimal Residual Disease (MRD)-negative, indicates that advanced techniques, such as flow cytometry or next-generation sequencing, cannot detect even one myeloma cell among a million healthy cells in the bone marrow. Achieving MRD-negativity is a key treatment goal, associated with improved outcomes.
How Remission is Confirmed
Confirming remission in multiple myeloma relies on a combination of specific clinical tests that assess various disease markers. Blood and urine tests detect and measure abnormal proteins produced by myeloma cells. Serum protein electrophoresis (SPEP) and immunofixation identify and quantify M-proteins, which are abnormal antibodies. The serum free light chain (FLC) assay measures the levels of light chain proteins, specifically kappa and lambda, and their ratio, with an imbalanced ratio indicating disease activity. In urine, these light chains are known as Bence-Jones proteins.
A bone marrow biopsy is another procedure, involving the extraction of a small sample of bone marrow from the hip bone. This sample is then examined under a microscope to count the percentage of plasma cells and identify any abnormal, clonal plasma cells.
Imaging scans are also used to assess the impact of myeloma on bones and other tissues. PET scans, CT scans, or MRIs help identify bone damage, such as lytic lesions or fractures, and detect plasmacytomas, which are tumors formed by myeloma cells outside the bone marrow. A full-body X-ray, known as a skeletal survey, can also be performed to check for widespread bone involvement.
Maintenance Therapy and Monitoring
Following the achievement of remission, many patients with multiple myeloma undergo maintenance therapy, an ongoing, less intensive treatment designed to extend the duration of remission and delay the potential return of the disease. This therapy aims to suppress any remaining myeloma cells undetectable by conventional tests. Medications used for maintenance therapy include lenalidomide, proteasome inhibitors like bortezomib or carfilzomib, or monoclonal antibodies such as daratumumab. The specific drug and its dosage are tailored to the individual patient, considering their prior treatments and disease characteristics.
Patients receiving maintenance therapy adhere to a regular monitoring schedule with their oncologist. These follow-up appointments involve routine blood and urine tests to track M-protein levels and free light chains. Imaging scans or bone marrow biopsies may also be performed periodically to detect any subtle signs of disease progression. Monitoring allows the healthcare team to identify changes in disease activity, enabling timely adjustments to the treatment plan.
Managing Relapse
Despite achieving remission, multiple myeloma is considered a chronic condition, and relapse, the return of the disease after a period of improvement, is part of its course. A relapse does not signify a failure of prior treatment, but indicates the disease has become active again. Clinicians and patients plan for this possibility, understanding that treatment strategies will evolve over time.
When relapse occurs, effective treatment options are available to bring the disease back under control. The choice of therapy depends on several factors, including the patient’s previous treatments, the duration of their remission, the aggressiveness of the relapse, and their overall health. Options may include adjusting the dose of previous maintenance drugs, adding new medications, or switching to entirely different drug combinations. New classes of drugs, such as bispecific antibodies and CAR T-cell therapies, are emerging for relapsed disease. A new treatment plan will be developed collaboratively between the patient and their medical team, aiming to achieve a new remission or control the disease for as long as possible.